Kristina Mladenovic's dip in form continued as the top seed suffered a shock second-round exit to Aliaksandra Sasnovich on a day of upsets at the Kremlin Cup.
The Frenchwoman suffered back-to-back first-round losses prior to featuring in Russia, defeats she called a "great lesson", and Mladenovic once again took an early tumble in a 6-2 2-6 6-2 reverse to the world number 100.
Sasnovich broke her opponent twice in a one-side opening set. Mladenovic's defence improved to level the match, but she was found wanting in the decider.
Coco Vandeweghe, seeded second, suffered a similar disappointment as the American slumped to a 7-5 1-6 6-2 defeat to Lesia Tsurenko.
Natalia Vikhlyantseva toppled third seed Elena Vesnina 7-6 (7-3) 6-4 and Irina-Camelia Begu claimed the scalp of fourth seed Anastasija Sevastova, winning 6-4 6-3.
Daria Gavrilova, a losing finalist in the early hours of Monday morning in Hong Kong, retired with a thigh injury when trailing 6-3 3-1 to Vera Lapko, while Maria Rybarikova - who beat Maria Sharapova on Tuesday - also withdrew when down 6-1 against Alize Cornet.
Julia Gorges and Daria Kasatkina were also winners in Moscow on Wednesday.
Third seed Anett Kontaveit went tumbling out of the Luxembourg Open as Heather Watson booked a quarter-final spot with a 6-4 6-4 victory.
Beatriz Haddad Maia was another seed to bow out in round two, going down 3-6 7-6 (7-5) 6-2 against Swede Johanna Larsson.
Kiki Bertens, the second seed, was 6-2 2-1 up when Andrea Petkovic retired, while Monica Puig, conqueror of Angelique Kerber on Tuesday, marched on with a 7-6 (7-2) 7-6 (7-1) win over Alison Van Uytvanck.
Elise Mertens, Carina Witthoeft, Pauline Parmentier and Naomi Broady also advanced to the last eight.